Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort

Mutations in the DMD gene, encoding the dystrophin protein, are responsible for the dystrophinopathies Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked Dilated Cardiomyopathy (XLDC). Mutation analysis has traditionally been challenging, due to the large gene size (79 exons over 2.2 Mb of genomic DNA). We report a very large aggregate data set comprised of DMD mutations detected in samples from patients enrolled in the United Dystrophinopathy Project, a multicenter research consortium, and in referral samples submitted for mutation analysis with a diagnosis of dystrophinopathy. We report 1,111 mutations in the DMD gene, including 891 mutations with associated phenotypes. These results encompass 506 point mutations (including 294 nonsense mutations) and significantly expand the number of mutations associated with the dystrophinopathies, highlighting the utility of modern diagnostic techniques. Our data supports the uniform hypermutability of CGA>TGA mutations, establishes the frequency of polymorphic muscle (Dp427m) protein isoforms and reveals unique genomic haplotypes associated with “private” mutations. We note that 60% of these patients would be predicted to benefit from skipping of a single DMD exon using antisense oligonucleotide therapy, and 62% would be predicted to benefit from an inclusive multiexonskipping approach directed toward exons 45 through 55. Hum Mutat 30:1657–1666, 2009. © 2009 Wiley-Liss, Inc.     

The Callender modification of the Macintosh laryngoscope blade reduces the risk of tooth-blade contact in children

Background: Dental injury is well recognized as a potential complication of laryngoscopy and tracheal intubation. The flange of the Macintosh blade may contact teeth during laryngoscopy causing damage. The Callander modification of the Macintosh blade (Callander blade) with a shortened heel at the proximal end has been shown to increase the blade–tooth distance and reduce contact rates in adults. Aim: This study was designed to evaluate the effectiveness of the Callander blade on reducing dental contact in children. Methods: One hundred children, aged 4–14 years, scheduled for general anesthesia requiring endotracheal intubation were studied prospectively. The children were preoperatively evaluated for Mallampati score and dental defects, looseness, and avulsions. Following induction of anesthesia, laryngoscopy was performed twice on each child in succession, once with a standard Macintosh blade and once with a Callander blade of the same size in a random order. The blade–tooth distance and contact rate were compared between the two blades. Results: With the Callander blade, the blade–tooth distance was greater than with the Macintosh (1.78 ± 1.77 vs 0.28 ± 0.76 mm, P = 0.001). The frequency of direct contact was less with the Callander blade than it was with the Macintosh blade (33% vs 86%, respectively, P = 0.008). However, difficult laryngoscopy rate did not differ between the blades. Tracheal intubation was successful in all children and there was no dental injury. Conclusion: Our findings suggest that the Callander blade decreases the risk for dental injury and provides tracheal intubating conditions in children with normal airways similar to those obtained with a traditional Macintosh blade.     

Receded near point of convergence as a predictor of mild cognitive impairment in the general geriatric population: results from a population-based study

AIM: To investigate the relationship between near point of convergence (NPC) and mild cognitive impairment (MCI) in the general elderly population. METHODS: The present report is a part of the Tehran Geriatric Eye Study (TGES): a population-based cross-sectional study conducted on individuals 60 years of age and above living in Tehran, Iran using the multi-stage stratified random cluster sampling method. Cognitive status was assessed using the Persian version of the Mini-Mental State Examination (MMSE). All study participants underwent complete ocular examination including measurement of uncorrected and best-corrected visual acuity, objective and subjective refraction, cover testing, NPC measurement, and slit-lamp biomicroscopy. RESULTS: The data of 1190 individuals were analyzed for this report. The mean age of the participants analyzed was 66.82±5.42 (60-92y) and 728 (61.2%) of them were female. Patients with MCI had a significantly more receded NPC compared to subjects with normal cognitive status (10.89±3.58 vs 7.76±2.71 cm, P<0.001). In the multivariable logistic regression model and in the presence of confounding variables, a receded NPC was statistically significantly associated with an increased risk of MCI (odds ratio: 1.334, 95% confidence interval: 1.263 to 1.410, P<0.001). According to receiver operating characteristic (ROC) analysis, a cut point NPC> 8.5 cm (area under the curve: 0.764, P<0.001) could predict the presence of MCI with a sensitivity and specificity of 70.9% and 69.5%, respectively. CONCLUSION: A receded NPC can be clinically proposed as a predictor of MCI in older adults. It is recommended that elderly with a receded NPC>8.50 cm undergo detailed cognitive screening for a definite diagnosis of MCI. In this case, the necessary interventions can be carried out to slow down MCI progression to dementia.     

Memantine administration in patients with optic neuritis: a double blind randomized clinical trial

Graefe's Archive for Clinical and Experimental Ophthalmology - As an inflammatory phenomenon, optic neuritis (ON) that causes demyelination in the optic nerve damages the retinal cells, and...     

Differential activation of mononuclear phagocytes in cerebellar malformation associated with Walker–Warburg syndrome

Walker–Warburg syndrome (WWS) is an autosomal recessive disorder with alterations affecting the CNS that are characteristic of type‐II lissencephaly and dysplasia/hypoplasia of the cerebellum. Other than these features, WWS is typically also accompanied by muscular dystrophy and abnormalities affecting the eyes. There is at present little information on the state of microglial and mononuclear phagocytic cell responses within the brain in WWS. In this case report, we present evidence for focal and differential activation of mononuclear phagocytes specifically confined to the dysplastic cerebellum of an infant at 5 months of age, diagnosed with WWS.     

Rechargeable aluminum batteries: effects of cations in ionic liquid electrolytes

Room temperature ionic liquids (RTILs) are solvent-free liquids comprised of densely packed cations and anions. The low vapor pressure and low flammability make ILs interesting for electrolytes in batteries. In this work, a new class of ionic liquids were formed for rechargeable aluminum/graphite battery electrolytes by mixing 1-methyl-1-propylpyrrolidinium chloride (Py13Cl) with various ratios of aluminum chloride (AlCl₃) (AlCl₃/Py13Cl molar ratio = 1.4 to 1.7). Fundamental properties of the ionic liquids, including density, viscosity, conductivity, anion concentrations and electrolyte ion percent were investigated and compared with the previously investigated 1-ethyl-3-methylimidazolium chloride (EMIC-AlCl₃) ionic liquids. The results showed that the Py13Cl–AlCl₃ ionic liquid exhibited lower density, higher viscosity and lower conductivity than its EMIC-AlCl₃ counterpart. We devised a Raman scattering spectroscopy method probing ILs over a Si substrate, and by using the Si Raman scattering peak for normalization, we quantified speciation including AlCl₄⁻, Al₂Cl₇⁻, and larger AlCl₃ related species with the general formula (AlCl₃)_n in different IL electrolytes. We found that larger (AlCl₃)_n species existed only in the Py13Cl–AlCl₃ system. We propose that the larger cationic size of Py13⁺ (142 ų) versus EMI⁺ (118 ų) dictated the differences in the chemical and physical properties of the two ionic liquids. Both ionic liquids were used as electrolytes for aluminum–graphite batteries, with the performances of batteries compared. The chloroaluminate anion-graphite charging capacity and cycling stability of the two batteries were similar. The Py13Cl–AlCl₃ based battery showed a slightly larger overpotential than EMIC-AlCl₃, leading to lower energy efficiency resulting from higher viscosity and lower conductivity. The results here provide fundamental insights into ionic liquid electrolyte design for optimal battery performance.

Room temperature ionic liquids (RTILs) are solvent-free liquids comprised of densely packed cations and anions. Properties of Py13Cl–AlCl₃ ILs were studied and compared with EMIC-AlCl₃ ILs for use as electrolyte in Al–graphite battery.     

Is simultaneous splenectomy an additive risk factor in surgical treatment for active endocarditis?

Purpose

Splenic abscess formation is a serious complication in the setting of active endocarditis, and splenectomy is recommended. However, the optimal timing for splenectomy is yet undetermined. The purpose of this study was to evaluate the role of a one-stage splenectomy and valve surgery for active endocarditis.

Methods

Among 202 consecutive endocarditis patients, 18 had splenic lesions on preoperative abdominal screening, who underwent cardiac surgery and splenectomy as a one-stage procedure (group A) and were compared to patients with unremarkable abdominal screening (group B, n?=?184) undergoing sole cardiac surgery.

Results

No difference was observed regarding preoperative characteristics (age, gender, New York Heart Association [NYHA] grade, diabetes, coronary artery disease, redo surgery, adiposity, smoking), intubation time, and prolonged ventilation. There were 23 early postoperative deaths in group B (12.5%) vs. none in group A. At 180?days, survival was significantly higher for patients in group A (94.4%) vs. group B (67.9%, p?=?0.016), although this difference did not reach statistical significance (log-rank test, p?=?0.073). Multivariate Cox proportional hazards regression revealed age above 50?years (hazard ratio [HR] 3.327, 95% confidence interval [CI] 1.279?C8.650) and NYHA class above III (NYHA III or IV: HR 3.117, 95% CI 1.119?C8.683, p?=?0.030; NYHA IV: HR 3.678, 95% CI 1.984?C6.817, p?<?0.001) as independent risk factors for mortality at 180?days. A trend towards a protective factor was observed for simultaneous splenectomy (HR?=?0.171, 95% CI 0.023?C1.255).

Conclusion

Simultaneous valve surgery and splenectomy is an approach for active endocarditis complicated by splenic lesions with a low 180-day mortality. Despite the expected risk elevation by septic lesions and the additive trauma of a laparotomy, patients with simultaneous splenectomy had a favourable outcome regarding early mortality and mortality at 6?months.